Technical Report Documentation Page
Carisoprodol (and Meprobamate)
Gamma-Hydroxybutyrate (GHB, GBL,
Lysergic acid diethylamide (LSD)
Methamphetamine (and Amphetamine)
Morphine (and Heroin)
Zolpidem (and Zaleplon, Zopiclone)
Biographical Sketches of Lead
Authors and Main Contributors
Methamphetamine hydrochloride is a white to light brown crystalline
powder, or clear chunky crystals resembling ice. Methamphetamine base
is a liquid.
Synonyms: Methamphetamine: chalk,
chrissy, crank, crystal, glass, go, hydro, ice, meth, rock candy, speed,
whiz; Desoxyn®; Amphetamine: dextroamphetamine; Dexedrine®,
Adderall®, Benzedrine®, DextroStat®, Biphetamine®, Gradumet®.
Source: The majority of street methamphetamine
is produced in clandestine laboratories (e.g. reduction of l-ephedrine
or d-pseudoephedrine over red phosphorus with hydroiodic acid,
or reduction with sodium or lithium in condensed liquid ammonia). Methamphetamine
remains concentrated in western U. S. states and some rural areas elsewhere. d-Methamphetamine
is a schedule II controlled substance (Desoxyn®) available in 5
mg white, 10 mg pink, and 15 mg yellow strength tablets. Amphetamine
is also a Schedule II controlled substance and is usually supplied as
the sulfate salt of the d-isomer (Dexedrine®), or as the
racemic mixture (Benzedrine®), or a mixture of the two (Adderall®).
Dexedrine® is available in 5, 10, and 15 mg strength, orange/black
capsules, or 5 mg tablets. Adderall® is available in 5, 7.5, 10,
12.5, 20, and 30 mg strength, blue or orange tablets.
Drug Class: CNS stimulant, sympathomimetic,
Medical and Recreational Uses: Medicinally,
methamphetamine is used in the treatment of narcolepsy, attention deficit
disorder (ADD), and attention deficit hyperactivity disorder (ADHD).
Typical doses are 10 mg/day or up to 40 mg daily, and a course of greater
than six weeks is not recommended. Methamphetamine is infrequently used
in the treatment of obesity, overeating disorders, and weight loss due
to its abuse potential. Amphetamine is also used in ADD, narcolepsy,
and weight control. Recreationally, methamphetamine is abused to increase
alertness, relieve fatigue, control weight, treat mild depression, and
for its intense euphoric effects.
Potency, Purity and Dose: Purity of methamphetamine
is currently very high, at 60-90%, and is predominantly d-methamphetamine
which has greater CNS potency than the l-isomer or the racemic
mixture. Common abused doses are 100-1000 mg/day, and up to 5000 mg/day
in chronic binge use. Therapeutic doses of Desoxyn® are 2.5-10 mg
daily, with dosing not exceed 60 mg/day. To treat narcolepsy, 5-60 mg/day
of amphetamine is ingested in divided doses; and in ADD and ADHD doses
of 2.5-10 mg/day is administered, depending on age.
Route of Administration: Methamphetamine
users often begin with intranasal or oral use and progress to intravenous
use, and occasionally smoking. In contrast to cocaine, the hydrochloride
salt of methamphetamine can itself be smoked. Methamphetamine is used
sometimes with alcohol or marijuana, particularly during the withdrawal
Pharmacodynamics: Methamphetamine increases
synaptic levels of the neurotransmitters dopamine, serotonin (5-HT)
and norepinephrine, and has a and b adrenergic agonist effects. Norepinephrine
is responsible for methamphetamine’s alerting, anorectic, locomotor
and sympathomimetic effects; dopamine stimulates locomotor effects,
psychosis, and perception disturbances; and 5HT is responsible for delusions
and psychosis. Methamphetamine’s effects are similar to cocaine
but its onset is slower and the duration is longer. Racemic amphetamine
and d-amphetamine have similar chemical properties and actions to methamphetamine
but are less potent.
Pharmacokinetics: Following oral administration,
peak methamphetamine concentrations are seen in 2.6-3.6 hours and the
mean elimination half-life is 10.1 hours (range 6.4-15 hours). The amphetamine
metabolite peaks at 12 hours. Following intravenous injection, the mean
elimination half-life is slightly longer (12.2 hours). Methamphetamine
is metabolized to amphetamine (active), p-OH-amphetamine and norephedrine
(both inactive). Several other drugs are metabolized to amphetamine
and methamphetamine and include benzphetamine, selegeline, and famprofazone.
Molecular Interactions / Receptor Chemistry: Methamphetamine
is metabolized to amphetamine via cytochrome P450 2D6. Potential inhibitors
of the 2D6 isoenzyme could decrease the rate of methamphetamine elimination
if administered concurrently, while potential inducers
could increase the rate of elimination.
Blood to Plasma Concentration Ratio: 0.65
Interpretation of Blood Concentrations: Blood
concentrations can generally be used to distinguish therapeutic use
from abuse. Concentrations of 0.02-0.05 mg/L are typical for therapeutic
use, and up to 0.2 mg/L have been documented. Concentrations greater
than this represent abuse. Concentrations do not disclose phase of use.
Normal concentrations in recreational use are 0.01 to 2.5 mg/L (median
0.6 mg/L). Concentrations above this range will likely be associated
with severe, possibly life threatening, toxicity. There is no evidence
for improved performance in any task or test following use of doses
greater than 40 mg (or concentrations greater than 0.2 mg/L).
Peak blood methamphetamine concentrations occur shortly after injection,
a few minutes after smoking, and around 3 hours after oral dosing. Peak
plasma amphetamine concentrations occur around 10 hours after methamphetamine
Interpretation of Urine Test Results: Positive
results generally indicate use within 1-4 days but could be up to a
week following heavy chronic use. Rate of excretion into the urine is
heavily influenced by urinary pH. Between 30-54% of an oral dose is
excreted in urine as unchanged methamphetamine and 10-23% as unchanged
amphetamine. Following an intravenous dose, 45% is excreted as unchanged
parent drug and 7% amphetamine.
Effects: Methamphetamine effects are less intense after oral ingestion
than following smoked or intravenous use. Early phase – Psychological:
Euphoria, excitation, exhilaration, rapid flight of ideas, increased
libido, rapid speech, motor restlessness, hallucinations, delusions,
psychosis, insomnia, reduced fatigue or drowsiness, increased alertness,
heightened sense of well being, stereotypes behavior, feelings of increased
physical strength, and poor impulse control. Early phase – Physiological: Increased heart rate, increased blood pressure, increased respiration
rate, elevated temperature, palpitations, irregular heartbeat, dry mouth,
abdominal cramps, appetite suppressed, twitching, pallor, dilated pupils,
HGN at high doses, faster reaction time, increased strength, and more
efficient glucose utilization. Late phase – Psychological: Dysphoria,
residual stimulation, restlessness, agitation, nervousness, paranoia,
violence, aggression, lack of coordination, pseudo-hallucinations, delusions,
psychosis, and drug craving.
Late phase – Physiological: Fatigue, sleepiness with
sudden starts, itching/picking/scratching, normal heart rate, and normal
to small pupils which are reactive to light.
Binge use of methamphetamine can be broken down into the following
phases: Rush – (5 minutes) intense euphoria, rapid flight of ideas,
sexual stimulation, high energy, obsessive/compulsive activity, thought
blending, dilated pupils; Shoulder –
(1 hour) less intense euphoria, hyperactivity, rapid flight of ideas,
obsessive/compulsive activity, thought blending, dilated pupils; Binge
use – (1-5 days) the drug is frequently readministered in an attempt
to regain or maintain euphoria; Tweaking – (4-24 hours) dysphoria,
scattered and disorganized thought, intense craving, paranoia, anxiety
and irritability, hypervigilance, auditory and tactile hallucinations,
delusions, and normal pupils; Crash – (1-3 days) intense fatigue,
uncontrollable sleepiness and catnapping, continuing stimulation, drug
craving; Normal – (2-7 days) apparent return to “normalcy” although
drug craving may appear; Withdrawal – anergia, anhedonia, waves
of intense craving, depression, hypersomnolence, exhaustion, extreme
Side Effect Profile: Light sensitivity, irritability,
insomnia, nervousness, headache, tremors, anxiety, suspiciousness, paranoia,
aggressiveness, delusions, hallucinations, irrational behavior, and
violence. In overdose, symptoms may include hyperthermia, tachycardia,
severe hypertension, convulsions, chest pains, stroke, cardiovascular
collapse, and possible death. Other common side effects following abuse
of amphetamines include viral hepatitis, Sexually Transmitted Diseases
(STDs), HIV, septicemia, abscesses, collapsed blood vessels, and malnutrition.
Chronic abuse generally produces a psychosis that resembles schizophrenia
and is characterized by paranoia, picking at the skin, preoccupation
with one’s own thoughts, and auditory and visual hallucinations.
Violent and erratic behavior is frequently seen among chronic abusers.
Over time, methamphetamine appears to cause reduced levels of dopamine,
which can result in symptoms like those of Parkinson’s disease.
Duration of Effects: Onset of effects is
rapid following intravenous use and smoking, while effects onset more
slowly following oral use. Overall effects typically last 4-8 hours;
residual effects can last up to 12 hours.
Tolerance, Dependence and Withdrawal Effect: Methamphetamine
has a high potential for abuse and dependence. Tolerance may develop
and users may quickly become addicted and use it with increasing frequency
and in increasing doses. Abrupt discontinuation of use can produce extreme
fatigue, mental depression, apathy, long periods of sleep, irritability,
Drug Interactions: Phenobarbital, propoxyphene,
phenytoin and MAOI’s slow the metabolism of amphetamines and increases
their effect on the release of norepinephrine and other monoamines from
adrenergic nerve endings. Amphetamines may counteract sedative effects
of antihistamines. Methamphetamine may restore ethanol induced impairment
in simple repetitive tasks of short duration, however, there is no restoration
of ethanol-induced deficits of balance and steadiness. In general, high
doses of amphetamines are likely to increase the impairing effects of
alcohol. Chlorpromazine and haloperidol block dopamine and norepinephrine
reuptake, thus inhibiting the central stimulant effects of amphetamines.
Amphetamine potentiates the analgesic effect of meperidine.
Performance Effects: Laboratory studies have
been limited to much lower doses than those used by methamphetamine
abusers. Doses of 10-30 mg methamphetamine have shown to improve reaction
time, relief fatigue, improve cognitive function testing, increase subjective
feelings of alertness, increase time estimation, and increase euphoria.
However, subjects were willing to make more high-risk choices. The majority
of laboratory tests were administered 1 hour post dose. Expected performance
effects following higher doses may include agitation, inability to focus
attention on divided attention tasks, inattention, restlessness, motor
excitation, increased reaction time, and time distortion, depressed
reflexes, poor balance and coordination, and inability to follow directions.
Effects on Driving: The drug manufacturer
states that patients should be informed that methamphetamine and amphetamine
may impair the ability to engage in potentially hazardous activities
such as driving a motor vehicle. In epidemiology studies drive-off-the-road
type accidents, high speed, failing to stop, diminished divided attention,
inattentive driving, impatience, and high risk driving have been reported.
Significant impairment of driving performance would also be expected
during drug withdrawal. In a recent review of 101 driving under the
influence cases, where methamphetamine was the only drug detected, blood
concentrations ranged from <0.05-2.36 mg/L (mean 0.35 mg/L, median
0.23 mg/L). Driving and driver behaviors included speeding, lane travel,
erratic driving, accidents, nervousness, rapid and non-stop speech,
unintelligible speech, disorientation, agitation, staggering and awkward
movements, irrational or violent behavior, and unconsciousness. Impairment
was attributed to distraction, disorientation, motor excitation, hyperactive
reflexes, general cognitive impairment, or withdrawal, fatigue and hypersomnolence.
DEC Category: CNS stimulant.
DEC Profile: Horizontal gaze nystagmus not
present; vertical gaze nystagmus not present; lack of convergence not
present; pupil size dilated; reaction to light slow; pulse rate elevated;
blood pressure elevated; body temperature normal to down. Other characteristic
indicators may include restlessness, body tremors, talkativeness, exaggerated
reflexes, anxiety, and track marks or recent injection sites.
Panel’s Assessment of Driving Risks: At
lower dose, amphetamines have few effects on cognitive functioning and
may result in an enhancement of some psychomotor tasks, but risk-taking
increases at higher doses and responses become inappropriate. Drug withdrawal
could also lead to the impairment of psychomotor skills required for
References and Recommended Reading:
Baselt RC. Drug effects on psychomotor performance. Biomedical
Publications, Foster City, CA; pp 30-5, pp 244-6;2001.
Forney R. Stimulants, drugs & driving, NIDA research monograph
11, ed by Willette, RE 1977:73-6.
Gygi MP, Gygi SP, Johnson M, Wilkins DG, Gibb JW, Hanson GR. Mechanisms
for tolerance to methamphetamine effects. Neuropharmacol 1996;35(6):751-7.
Hurst PM. Amphetamines and driving. Alc Drugs Driv 1987;3(1):13-6.
Jerome L, Segal A. Benefit of long-term stimulus on driving in adults
with ADHD. J Nerv Ment Dis 2001(1);189:63-4.
Logan BK. Amphetamines: an update on forensic issues. J Anal Toxicol 2001;25(5):400-4.
Logan BK. Methamphetamine and driving impairment. J Forensic Sci 1996;41(3):457-64.
Logan BK. Methamphetamine - Effects on Human Performance and Behavior. Forens
Sci Rev 2002;14(1/2):133-51.
National Transportation Safety Board safety study: Fatigue, alcohol,
other drugs, and medical factors in fatal-to-the-driver heavy truck
crashes (vol I and II). Accession# PB90-917002, report# NTSB/SS-90/01/02,
National Transportation Safety Board, Washington DC, 1990.
Perez-Reyes M, White WR, McDonald SA, Hicks RE, Jeffcoat AR, Hill JM,
Cook CE. Clinical effects of daily methamphetamine administration. Clin
Physicians’ Desk Reference, Medical Economics Company,
Montvale, NJ, 2002.
Smith DE, Fischer CM. An nalysis of 310 cases of acute high dose methamphetamine
toxicity in Haight-Ashbury. Clin Toxicol 1970;3(1):117-24.